CN111511657A

CN111511657A - Auto-injector kit for reducing oxygen in packaging

Info

Publication number: CN111511657A
Application number: CN201880082987.2A
Authority: CN
Inventors: 塞巴斯蒂安·赫尔穆特·约瑟·鲍尔
Original assignee: Ingert Pharmaceutical Sweden Ltd
Current assignee: Ingert Pharmaceutical Sweden Ltd
Priority date: 2017-12-21
Filing date: 2018-12-21
Publication date: 2020-08-07
Anticipated expiration: 2038-12-21
Also published as: EP3728071A1; WO2019122367A1; AU2018386656A1; CN111511657B; US20210077710A1; CA3084889A1

Abstract

The present invention relates to a packaged auto-injector kit. The packaged auto-injector kit comprises a partially transparent medicament container, a hollow auto-injector body forming an auto-injector with the medicament container and an oxygen-impermeable package (2) having an opening arrangement (3) for opening the package (2). The auto-injector body has at least two apertures (4) to allow visual control of the pharmaceutical composition, at least a portion of the package (2) is transparent for visual control of the pharmaceutical composition, and the packaged auto-injector kit comprises at least one blocking arrangement (5) which is opaque to at least ultraviolet light. The invention also relates to a method for filling packages (2) with an automatic syringe. The method comprises inserting an automatic injector into the package (2) in a non-inert environment and at atmospheric pressure, replacing the air in the package (2) with an inert atmosphere by one or more cycles of removing the air and filling it with an inert gas through an opening. The opening was sealed under vacuum.

Description

Auto-injector kit for reducing oxygen in packaging

Technical Field

The present invention relates to an automatic injector for administering epinephrine and a method of filling a package with the automatic injector.

Background

Autoinjectors are intended for self-administration. There are many designs of auto-injectors, but common is that they all work to overcome the hesitation associated with self-administration. They are typically needle-based devices with preloaded syringes. Before use, the needle is shielded to avoid injuring oneself.

Not only does the function need to be considered when designing an auto-injector. Usability is also important because autoinjectors are often used by personnel untrained in their use. It is very clear to the person who picks up the device how to use it. For example, epinephrine auto-injectors for use by people at risk of anaphylaxis are typically used under time pressure, and it is important that patients receive injections quickly after exposure to the allergen. In this case, it is more important that the auto-injector is easy to use and self-explanatory in design.

Another problem with designing autoinjectors is that the life of the drug is affected by the design. For example, some drugs are very sensitive to oxygen, all are sensitive to plunger movement during transport, as sterility is compromised, and some are sensitive to light. Oxidative degradation is a chemical process that renders many drugs inactive by degrading the active ingredient, or renders the product unusable by changing the properties of the excipients or by changing some or all of the physical properties. In addition, oxidation can negatively affect the plastic components of the auto-injector, thereby reducing the reliability and shelf life of the mechanical auto-injector.

Autoinjectors are typically packaged in protective packaging to protect them prior to use. For drugs that are sensitive to oxygen and/or other atmospheric gases, the packaging process for automatic injectors is very important and often cumbersome.

There is a need to simplify the process of packaging an automatic injector while providing an automatic injector that is easy to use and exhibits a long shelf life for the drug.

Disclosure of Invention

It is an object of the present invention to at least partially overcome the above problems and to provide an improved auto-injector and a method for packaging an auto-injector.

The present disclosure aims to provide a packaged auto-injector, the usability of which is increased and the packaging process of which is more user-friendly.

This object is achieved by a device as defined in claim 1 and a method as defined in claim 14.

According to one embodiment of the present disclosure, a packaged automatic injector kit is included for providing a packaged automatic injector comprising an epinephrine composition. The auto-injector kit comprises: an at least partially transparent pharmaceutical container comprising an epinephrine composition; a hollow auto-injector body defining a space for receiving a medicament container and thereby forming an auto-injector; and an oxygen impermeable package for receiving the auto-injector and which includes an opening arrangement for opening the package to remove the auto-injector. The auto-injector body is provided with at least two apertures, said apertures being provided on opposite sides of the medicament container to allow visual control of the epinephrine composition inside the container; at least a portion of the wrapper is transparent to visible light to allow visual control of the epinephrine composition through the aperture; the packaged auto-injector kit comprises at least one blocking arrangement that is at least opaque to ultraviolet light, the blocking arrangement being arranged to prevent ultraviolet light from entering the at least two apertures. Thus, the packaged auto-injector kit allows visual control of the epinephrine composition and the barrier arrangement protects the drug from ultraviolet light. It should be noted that the packaged auto-injector kit may be used with any pharmaceutical composition and is not limited to epinephrine. Exposure to uv light may cause the pharmaceutical composition to decompose or undergo molecular changes. In other words, the ultraviolet light is prevented from entering the two holes and thus does not affect the epinephrine.

According to some aspects, the at least one blocking arrangement is disposed on the auto-injector body and comprises at least one film placed over the at least two apertures, wherein the film is transparent to visible light and opaque to ultraviolet light. This arrangement ensures that both packaged and unpackaged autoinjectors prevent uv light from entering both apertures. In other words, this arrangement protects the pharmaceutical composition before packaging, while packaging, and after opening the package and removing the automatic injector.

According to some aspects, the at least one blocking arrangement is arranged on a visible light transparent portion of the package, and the at least one blocking arrangement comprises a layer transparent to visible light and not transparent to ultraviolet light on the transparent portion. Thus, the ultraviolet light is prevented from entering both holes, but the package is still see-through to allow visual control of the pharmaceutical composition. This blocking arrangement blocks ultraviolet light without the need for a blocking arrangement to be arranged on the auto-injector.

According to some aspects, at least one blocking arrangement is arranged on the package, and wherein the transparent portion of the package is closable such that the package is opaque to both visible and ultraviolet light when the transparent portion is closed, thereby blocking the visible and ultraviolet light from entering the at least two apertures. Depending on the pharmaceutical composition, the sensitivity to ultraviolet light may vary. Some pharmaceutical compositions are also sensitive to visible light, such as epinephrine. Thus, a blocking arrangement may be arranged to prevent both ultraviolet and visible light from entering the aperture.

According to some aspects, the transparent portion is arranged on a first side of the wrapper and the wrapper has a second side which is opaque to uv and visible light, wherein the blocking arrangement comprises a fold (folding) of the second side of the wrapper on the first side of the wrapper to cover the transparent portion to block uv and visible light from entering the at least two apertures. In other words, the wrapper is foldable and when folded, the opaque side covers the transparent side. It should be noted that if the transparent portion is large, the fold may not cover the entire transparent area, but the opaque portion must cover at least the transparent portion located above the two holes.

According to some aspects, the opening arrangement is positioned such that it is not covered when the wrapper is folded. That is, the opening arrangement should not be blocked by the blocking arrangement.

According to some aspects, the opening arrangement is arranged to be torn by a user thereof, such that the package tears, and wherein the opening arrangement comprises a stop (stop) which prevents the user from tearing the package completely, such that a portion remains when the package is torn. The stopper is for example a thick portion of the package which is not easily torn. The stop may also be another material in the package that prevents tearing. There is a great risk that the user will drop the auto-injector if the opening of the package is not controlled. If the user tears open the package and easily opens it completely, the user may not be ready to grasp the automatic injector. The opening arrangement is for example pre-cut or two sides of the package glued together so that they will tear apart from each other.

According to some aspects, the stopper comprises an increased tear resistance in the package. Tear resistance can be affected in a variety of ways; for example, the use of thicker sections of the wrapper or the use of other materials makes it difficult to tear the wrapper.

According to some aspects, the opening arrangement comprises a primary opening arrangement for opening the package and a secondary opening arrangement for opening the package if it cannot be opened by the primary opening arrangement. Since safe and quick removal of the auto-injector may be critical to the patient, the secondary opening arrangement may be used as a back-up if there is a problem with the primary opening arrangement. The primary and secondary opening arrangements may be different types of opening arrangements or the same type of opening arrangement.

According to some aspects, the opening arrangement comprises a pre-cut. The pre-cut is easy for the user to understand and it is therefore self-evident to the user how to open the package to remove the auto-injector.

According to some aspects, the wrapper is rectangular in shape and the pre-cut is located on one of the longer sides of the rectangle. If the cut-out is located on the shorter side, the opening of the package may result in the opening being too small to remove the auto-injector therefrom.

According to some aspects, the wrapper comprises two sides, a first side and a second side, connected to each other and wherein the two sides are openably connected such that a user tears the two sides apart when opening the wrapper. Such an opening arrangement is also something that the user has seen before and can easily use. The two sides are for example welded together.

According to some aspects, the package comprises an upper half and a lower half, and wherein the auto-injector body comprises a first end comprising the cap and a second end, the auto-injector being housed in the package such that the first end is located in the lower half of the package and the opening arrangement is arranged in the upper half of the package. In this way, the lidded side of the auto-injector is not the end that the user first pulls out of the package to prevent accidental opening of the lid when the auto-injector is withdrawn.

According to some aspects, the unopened package is filled with an inert gas and is free of oxygen capture agent (oxygen capture substance). The elimination of the need for an oxygen capture agent to capture residual oxygen in the package is a result of the packaging process disclosed herein. This may save costs and materials.

According to some aspects, the epinephrine composition comprises an oxygen scavenger. Chemical oxygen scavengers are used to prevent oxidative degradation of pharmaceutical compositions. It also serves to extend the shelf life of the automatic injector.

According to some aspects, the oxygen scavenger comprises sodium metabisulfite. Sodium metabisulfite is an effective oxygen scavenger.

According to some aspects, the concentration of sodium metabisulphite in the epinephrine composition is less than or equal to 0.21mg/m L it is desirable to use as little sodium metabisulphite as possible as it affects the pharmaceutical composition.

According to some aspects, the auto-injector body is elongate having an elongate portion, a first end side and a second end side opposite the first end side, and the at least one through-hole is arranged through the auto-injector body between the first end side and the second end side such that when the auto-injector body contains a medicament container, the at least one through-hole allows airflow through the auto-injector body, and the pack is a bag, the interior of the bag being at least 70mm longer than the overall length of the auto-injector, and the maximum width of the bag at the narrowest being 30mm wider than the maximum width of the auto-injector. An advantage of an auto-injector having a through-hole between the end sides is that the package can be made narrower than conventional packages. This is because air behind the auto-injector will be expelled through the through-holes rather than through the sides of the auto-injector. This reduces the amount of packaging required and also makes the packaged auto-injector easier for the end user to handle.

According to some aspects, the package filled with the autoinjector is tightly arranged in a neoprene sleeve, thereby preventing the autoinjector from moving relative to the package. The neoprene sock protects the packaged auto-injector from physical damage, keeps the temperature of the auto-injector more constant, and minimizes movement of the packaged auto-injector, thereby minimizing friction that could cause a puncture. In the case of packaging using an auto-injector with a through hole and a narrower bag, there will not be much packaging material around the auto-injector. The packaged automatic injector kit is easily stored in a neoprene cover; it does not need to hold many packages when it is placed in the sleeve.

The present disclosure also includes a method of filling a package with an automatic injector comprising an epinephrine composition, the package including an opening. The epinephrine composition may comprise a chemical oxygen scavenger. The method includes inserting an automatic injector into the package through the opening in a non-inert environment and displacing the air in the package with an inert atmosphere in the non-inert environment and at atmospheric pressure through one or more cycles of removing the air and filling the opening with an inert gas. The method also includes sealing the opening under vacuum. This method has the great advantage that it can be carried out in a non-inert environment. Maintaining an inert environment for packaging is very expensive and cumbersome.

According to some aspects, air is removed using a nozzle sealing machine (vacuum sealing machine). Such machines have a nozzle which can be inserted into the opening of the package and through which air is discharged. Such machines provide a local point in the opening to remove air, which is an effective way to remove only the air in the package.

Drawings

The invention will now be explained in more detail by describing different embodiments of the invention and with reference to the drawings.

FIG. 1 illustrates an example of an auto-injector, in which the orifice is shown;

FIG. 2 illustrates an example of a packaged auto-injector kit showing a hole visible through the package;

figure 3 shows an example of a package with a pre-slit opening;

figure 4 shows an example of a wrapper with a tear opening;

FIG. 5 shows an example of a package having a primary opening and a secondary opening;

FIG. 6 shows an example of a package having primary, secondary and tertiary openings;

FIG. 7 shows an example of a packaged auto-injector kit, with arrows indicating how to fold the package to close the stopper arrangement;

FIG. 8 shows an example of a packaged auto-injector kit in which the package has been folded;

FIG. 9 shows an example of a packaged auto-injector kit in which the package has been folded in two places;

figure 10 shows an example of a cross-sectional view of an auto-injector having an enlarged portion;

FIG. 11 illustrates an exemplary package for an automatic injector;

FIG. 12 shows a block diagram of the method;

figure 13 shows an exemplary shape of a package for an auto-injector;

figure 14 shows an exemplary shape of a package for an auto-injector;

fig. 15 shows an example of a nozzle type vacuum capper.

Detailed Description

Aspects of the present disclosure are described more fully hereinafter with reference to the accompanying drawings. The apparatus and methods disclosed herein may, however, be embodied in many different forms and should not be construed as limited to the aspects set forth herein. Like reference symbols in the various drawings indicate like elements throughout.

The terminology used herein is for the purpose of describing particular aspects of the disclosure only and is not intended to be limiting of the invention. As used herein, the singular forms "a", "an" and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise.

Unless otherwise defined, all terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs.

The term "epinephrine (adrenaline) composition" is defined as a composition comprising epinephrine (also known as epinephrine) and salts thereof. Such salts include, but are not limited to, epinephrine tartrate and epinephrine hydrochloride.

Fig. 1 shows a schematic representation of an auto-injector 1, in which two holes 4 for visual control of the inner medicament are shown, and fig. 2 shows when such an auto-injector is packed in a package 2. Grips (grip)10 are also provided on the sides of the syringe to provide a good grip for the user when operating the auto-injector. The grip is for example a rubber ridge.

The present disclosure provides a packaged autoinjector kit 6 for providing a packaged autoinjector 1 comprising an epinephrine composition. The auto-injector kit includes an at least partially transparent drug container containing an epinephrine composition. Other common terms for drug containers are primary packaging (primary packaging) and primary container (primary container). The medicament container is for example a syringe. The syringe may be spring loaded to push it out when injecting the medicament. The medicament container is, for example, a prefilled syringe having a spike (lanced-on needle) and having oxygen permeability, e.g. a prefillable syringe with a spike and a rigid or flexible needle shield sterilized by EtO and thus permeable to oxygen. Oxygen permeable primary containers are very common because sterilization is usually performed by EtO gas, whereas sterilization requires gas permeability of e.g. a needle shield. Other sterilization methods have other disadvantages. Radiation sterilization can discolor glass and autoclaving only allows the use of large volume syringes. Various types of drug containers may be used in the autoinjector, and it is not critical to the present disclosure which container is used. It should be noted that other pharmaceutical compositions besides epinephrine may be used in the disclosed packaged automatic injector kit 6. The packaged auto-injector kit according to the present invention is suitable for use with epinephrine because it is easy to open, easy to use and the shelf life of the auto-injector is long. In other words, the auto-injector is an epinephrine auto-injector.

The primary container may be filled with a drug product without air bubbles (if drug viscosity permits) or a drug product containing inert gas bubbles, and may be sterile or sterilized by terminal sterilization, the drug formulation may contain an oxygen scavenger, such as sodium metabisulfite, ascorbic acid, etc., if residual oxygen, which is normally unavoidable during filling and packaging, must be scavenged, thus, according to some aspects, the epinephrine composition contains a chemical oxygen scavenger for preventing oxidative degradation of the drug composition, oxidative degradation is a chemical process that renders many drugs inactive by degrading the active ingredient or rendering the product unusable by changing the properties of the excipients or changing the physical properties of the liquid container or device, it serves to increase the shelf life of the autoinjector 1, according to some aspects, the chemical oxygen scavenger includes sodium metabisulfite, sodium metabisulfite is an effective chemical oxygen scavenger, according to some aspects, the concentration of sodium metabisulfite in the epinephrine composition is less than or equal to 0.21mg/m L, such as less than 0.2, 0.18 or 0.16mg/m L, preferably, the concentration of sodium metabisulfite in the epinephrine composition is less than or equal to 0.15mg/m, even more preferably less than 0.15 mg/15 mg/m, even more preferably, this is less than the concentration of an allergen in an allergen resistant to a pharmaceutical composition that would be able to minimize the shelf life that would be able to cause a pharmaceutical composition such as would be able to cause a person who may be able to suffer from an allergic reaction in an allergic reaction, such as a person who is able to a person who has had an allergic reaction, such as had a person who had an allergic reaction, such as had a person who had an allergic reaction, or had a person who had a person who had a person who had a person who had a person who had a person who had a person.

The hollow auto-injector body defines a space in which a medicament container is accommodated and thus forms the auto-injector 1. The shape of the auto-injector body may be adapted to accommodate different kinds of medicament containers. According to some aspects, the auto-injector body is also adapted to accommodate other parts of the auto-injector 1, such as a spring, if a spring-loaded injector is present. As another example, if the auto-injector is a gas jet auto-injector that uses pressurized gas to propel a fine jet of medicament through the skin of a patient without the use of a needle, the auto-injector body may house a pressurized gas container.

It should be noted that other types of medical injection devices than autoinjectors may be used within the scope of the present disclosure. In other words, the present disclosure may be applied to any medical injection device, including auto-injectors.

The auto-injector is packaged in an oxygen-impermeable package 2 to contain the auto-injector and includes a cover for the auto-injectorOpening the package 2 to remove the opening arrangement 3 of the auto-injector oxygen impermeable package means that less than 1m L O is allowed to be present within 3 years₂Preferably, oxygen-impermeable packaging means that less than 0.1m L O is allowed to be present within three years₂The package of (1). It is almost impossible to provide a completely oxygen impermeable package.

The auto-injector body is provided with at least two apertures 4 arranged on opposite sides of the medicament container to allow visual control of the epinephrine composition within the container. Two or more control windows (i.e. holes) will allow visual control using light from behind to improve controllability of e.g. particles and/or fading. Visual control of the drug composition (i.e., the drug in the automatic injector) is important so that the user can easily check whether there is a problem with the drug; for example, if the container is ruptured, leakage of the drug may result, or the drug may discolor, for example, due to oxygen exposure or particle formation.

At least a portion of the package 2 is transparent to visible light to allow visual control of the epinephrine composition through the aperture 4, and the packaged auto-injector kit 6 comprises at least one blocking arrangement 5, which is at least opaque to ultraviolet light, arranged to prevent ultraviolet light from entering the at least two apertures 4. The blocking arrangement 5 may be arranged on the auto-injector body or the pack. Thus, the packaged auto-injector kit allows visual control of the pharmaceutical composition and the blocking arrangement 5 protects the drug from uv light. Exposure to uv light may result in photodegradation changes of the pharmaceutical composition. In other words, the uv light is prevented from entering the two holes, so that the pharmaceutical composition is not affected.

The blocking arrangement 5 may be implemented in some different ways. According to some aspects, the at least one blocking arrangement 5 is arranged on the auto-injector body and comprises at least one film placed over the at least two apertures 4, wherein the film is transparent for visible light and opaque for ultraviolet light. The membrane may be, for example, an adhesive label that is adhered to the body of the automatic injector over the aperture. The membrane is one membrane or two membranes large enough to cover two holes, one for each hole. In addition, the film is part of an automatic injector label, so uv protection and labeling can be done in one step. This arrangement ensures that both packaged and unpackaged autoinjectors prevent uv light from entering the two apertures. In other words, this arrangement protects the pharmaceutical composition before packaging, while packaging and after opening package 2 and removing the auto-injector.

Another example of a blocking arrangement 5 is that at least one blocking arrangement 5 is arranged on a visible light transparent part of the package 2 and comprises in the transparent part a layer transparent to visible light and opaque to ultraviolet light. Thus, the ultraviolet light is prevented from entering the two holes 4, but the package 2 can still be seen through to allow visual control of the pharmaceutical composition. Such a blocking arrangement 5 does not require a blocking arrangement 5 on the auto-injector to block the ultraviolet light.

The sensitivity to ultraviolet light may vary depending on the pharmaceutical composition. Some pharmaceutical compositions are also sensitive to visible light. Thus, the blocking arrangement 5 may be arranged to prevent both ultraviolet and visible light from entering the aperture 4. According to some aspects, at least one blocking arrangement 5 is arranged on the wrapper 2, and wherein the transparent portion of the wrapper 2 is closable such that the wrapper 2 is opaque to visible and ultraviolet light when closing the transparent portion, thereby preventing the visible and ultraviolet light from entering the at least two apertures 4. One example aspect is a pouch constructed from two different foils that are welded together to form the pouch. Such a pouch is shown in figures 7-9 with the opaque foil underlying the auto-injector, thus showing the visibility of the auto-injector (unless portions have been folded, in which case the opaque portions are shown in black and the covered portions of the auto-injector are not visible in the figures).

There are a number of ways to provide a closable transparent portion. According to some aspects, the transparent portion is arranged on a first side of wrapper 2, and wrapper 2 has a second side that is opaque to uv and visible light, wherein blocking arrangement 5 comprises a fold of the second side of wrapper 2 over the first side of wrapper 2 to cover the transparent portion, thereby preventing uv and visible light from entering the at least two apertures 4. In other words, the wrapper is foldable, with the opaque side covering the transparent side when folded. Such an example is shown in figures 7 and 8, where figure 7 shows the wrapper before folding and figure 8 shows the wrapper after folding. In the example shown, one side of the package is transparent and the other side is opaque. It should be noted that if the transparent portion is large, the fold may not cover the entire transparent area, but the opaque portion must cover at least the transparent portion located above the two holes 4. This is the case in the example of fig. 7 and 8. Another example of a closable transparent portion is that the transparent portion comprises two transparent portions arranged on both sides of the package such that each transparent portion is located above an aperture of the auto-injector body, and the blocking arrangement 5 comprises a fold of the package in two positions such that the transparent portions are covered by portions of the package that are opaque to ultraviolet and visible light, thereby preventing the ultraviolet and visible light from entering the at least two apertures. Another example is shown in fig. 9, where both sides of the package are folded over the autoinjector as shown.

The folding of the package 2 should not affect the accessibility of the auto-injector and therefore, according to some aspects, the opening arrangement 3 is positioned such that it is not covered when the package 2 is folded. I.e. the opening arrangement 3 should not be blocked by the blocking arrangement 5. This can be achieved by designing wrapper 2 such that wrapper 2 is not folded in the middle, but is biased to one side of the wrapper. Thus, not the entire wrapper is in the folded portion. In fig. 9, an opening arrangement in the form of a pre-cut is shown, which opening is arranged at the opposite end of the package to the blocking arrangement.

The blocking arrangement 5 may also be arranged as a flap (flap) covering the transparent portion. Thus, according to some aspects, the at least one blocking arrangement 5 comprises a cover sheet arranged above the transparent portion, the cover sheet being adapted to be lifted to allow visual control of the adrenergic composition. According to some aspects, the transparent portion comprises two transparent portions on both sides of the package 2, and wherein the at least one blocking arrangement 5 comprises two cover flaps arranged respectively above the transparent portions, each cover flap being adapted to be lifted to allow visual control of the pharmaceutical composition.

If the opening of package 2 is not controlled, there is a significant risk that the user will drop the auto-injector. If the user tears open the package and is ready to open it completely, the user may not be ready to grasp the automatic injector. Medicament containers made of glass are commonly used, which are particularly sensitive to dropping of the auto-injector. Plastic drug containers may be more durable but may pose other problems with regard to the purity of the drug located within. According to some aspects, the opening arrangement 3 is arranged to cause the package 2 to tear when torn by a user, and wherein the opening arrangement 3 comprises a stop which prevents the user from tearing the package 2 completely such that a portion remains when the package 2 is torn. The stopper is, for example, a thick portion of package 2 that is not easily torn open. The stop may also be another material in the package that prevents tearing. The opening arrangement 3 is for example pre-cut or two sides of a package glued together so that they will tear apart from each other. When the opening arrangement 3 is two sides tearably glued together, the stop can be such that: the adhesive at the stop is different from the adhesive at the tear away portion and the adhesive at the stop is stronger. According to some aspects, wrapper 2 comprises two sides, a first side and a second side, connected to each other, and wherein the two sides are openably connected such that a user tears the two sides apart when opening wrapper 2. Such an opening arrangement 3 is also something that the user has seen before and can easily use. The peel strength of such a solution may be, for example, about 0.18kg/cm or 1 lb./inch. Figure 3 shows an example of a package 2 with a precut opening and figure 4 shows an example of a package 2 with a tear opening.

According to some aspects, the stop comprises an increased tear resistance in package 2. The tear strength should be optimised to minimise the risk of the bag being torn completely and thus to minimise the risk of the auto-injector falling to the ground. Tear resistance can be affected in a number of ways; for example, using a thicker portion of wrapper 2, using another material makes it more difficult to tear wrapper 2, or using a strong adhesive as described above. An alternative to the stop is that it comprises an adhesive label placed on package 2, so as to prevent package 2 from opening at the adhesive label.

As discussed previously, the opening arrangement 3 comprises, for example, a pre-cut. The pre-cut is easy for the user to understand and it is therefore self-evident to the user how to open package 2 to remove the auto-injector. According to some aspects, wrapper 2 is rectangular in shape, and the pre-cut is located on one of the longer sides of the rectangle. If the cut-out is located on the shorter side, the opening of package 2 may result in the opening being too small to remove the auto-injector therefrom. Packages that have been adapted for a particular auto-injector may have a minimum size which results in short ends of the packages being approximately 1/2-1/3 of the long side of the package. The shape of the wrapper may be rectangular and may have rounded corners to give an oval shape.

Since safe and quick removal of the auto-injector may be of vital importance for the patient, the secondary opening arrangement 3 "may be used as a back-up arrangement if there is a problem with the primary opening arrangement 3'. Thus, according to some aspects, opening arrangement 3 comprises a primary opening arrangement 3 'for opening packages 2 and a secondary opening arrangement 3 ″ for opening packages 2 in case they cannot be opened by primary opening arrangement 3'. Figure 5 shows an exemplary package 2 having a primary opening and a secondary opening. The primary and secondary opening arrangements may be different types of opening arrangements as shown in fig. 5, or may be the same type. For example, as shown, the primary opening arrangement 3' comprises a pre-cut, and the secondary opening arrangement 3 "comprises a wrapper having two sides which are torn or in other words pulled apart at the opening, or vice versa. Fig. 6 also shows an example with a three opening arrangement.

One end of the automatic injector may be better grasped by the user when pulling the automatic injector from the package after opening the package. According to some aspects, the pack 2 comprises an upper half and a lower half, and wherein the auto-injector body comprises a first end comprising the lid and a second end, the auto-injector being accommodated in the pack 2 such that the first end is located in the lower half of the pack 2, the opening arrangement 3 being arranged in the upper half of the pack 2. In other words, the opening arrangement 3 is placed in the upper 50% portion of the bag. According to some aspects, the opening arrangement is placed in the upper 40% portion of the bag. According to some aspects, the opening arrangement is placed in an upper 30% portion of the bag. According to some aspects, the opening arrangement is placed in the upper 20% portion of the bag. According to some aspects, the opening arrangement is placed in the upper 10% portion of the bag. In this way, the lidded side of the auto-injector is not the end that the user first pulls out of the package to prevent accidental opening of the lid when the auto-injector is withdrawn. When the opening arrangement 3 comprises a primary opening arrangement and a secondary opening arrangement 3, it is more important for the primary arrangement, since the secondary arrangement is a back-up arrangement.

According to some aspects, the unopened package 2 is filled with an inert gas and is free of oxygen capture agent. The elimination of the need for an oxygen capture agent to capture residual oxygen in the package is a result of the packaging process disclosed herein. Preferably, unopened package 2 contains less than 2% oxygen, more preferably less than 1% oxygen. According to this aspect, some drugs will have an acceptable shelf life, and some drugs may require an oxygen scavenger, such as an oxygen scavenger, to achieve an acceptable shelf life. Having a package without oxygen traps can save costs, simplify the packaging process, provide a more stable product, and save materials.

Fig. 10 shows a cross-sectional view of an exemplary auto-injector, wherein the auto-injector has a through-hole opening 81 in the through-hole 8, according to the following. In this example, the through-hole opening is arranged in the end-side recess 9. The through-hole opening may also be arranged at a substantially flat end side. The top view shows the location of the incision made at X in the auto-injector. Y and Z are enlarged portions of the middle of the end portion for showing an enlarged view of the through-hole opening 81.

According to some aspects, the auto-injector body 7 is elongate having an elongate portion, a first end side 71 and a second end side 72 opposite the first end side 71, and the at least one through hole 8 is arranged through the auto-injector body 8 between the first and second end sides 71,72 such that when the auto-injector body 7 contains a medicament container, the at least one through hole 8 allows gas to flow through the auto-injector body 7; and the encasement is a bag, the interior of the bag being at least 70mm longer than the overall length of the auto-injector, the maximum width of the bag at the narrowest being 30mm wider than the maximum width of the auto-injector. An advantage of an auto-injector having a through-hole between the end sides is that the package can be made narrower than conventional packages. This is because air behind the auto-injector will be expelled through the through-holes rather than through the sides of the auto-injector. This reduces the amount of packaging required and also makes the packaged auto-injector easier for the end user to handle. According to some aspects, the interior of the bag is at least 80 or 90mm longer than the overall length of the autoinjector. This is to avoid wrinkling of the package during the packaging process, as will be explained further below.

Each of the at least one through-hole 8 comprises two through-hole openings 81. In other words, each through hole has an opening at each end of the auto-injector. It should be noted that if there is more than one through hole, they may share the same opening through the auto-injector, but have different openings on the end side.

The package filling the auto-injector may be tightly arranged in a neoprene cover to prevent the auto-injector from moving relative to the package. The neoprene sock protects the packaged auto-injector from physical damage, keeps the temperature of the auto-injector more constant, and minimizes movement of the packaged auto-injector, thereby minimizing friction that could cause a puncture. In the case of packaging using an auto-injector with a through hole and a narrower bag, there is not much packaging material around the auto-injector. The packaged automatic injector kit is easy to store in a neoprene cover; it does not need to hold many packages when it is put into the sleeve. The neoprene sock protects the packaged auto-injector from physical damage, keeps the temperature of the auto-injector more constant, and minimizes movement of the packaged auto-injector, thereby minimizing friction that could cause a puncture. The neoprene cover is latex.

Another expression for the through-hole is a gas passage, as the through-hole is a passage that allows gas to flow from one end side of the autoinjector to the other end side. In other words, the at least one through hole is an uninterrupted passage to allow gas to flow from one end side of the autoinjector to the other end side. The through-hole, i.e., the gas passage, is a hole that passes through the auto-injector body from one end side to the other end side, also from one end side to the other end side when the medicine container is located in the auto-injector body. It should be noted that the at least one through hole need not be a straight hole through the auto-injector, but only a through hole between the end sides, or in other words a gas passage between the end sides.

It should be noted that there are many different designs of auto-injectors which accommodate different kinds of medicament containers. The present disclosure is applicable to all types of automatic injectors having prefilled drug containers. For narrow bags, it is desirable that the auto-injector have a through hole so that air can be drawn from the bag by the auto-injector.

An exemplary wrapper is shown in fig. 11. This figure is merely an example and the measurements will be adjusted depending on the size of the auto-injector and which type of method is used to remove air from the package. The example of figure 11 is a bag with a width a of 95mm and a length B of 307 mm. This exemplary bag is used for an automatic injector having a length of 150 + -1 mm and a width of 23.4 to 27.4 + -0.5 mm. The seal width C was 10mm, being the seal between the two sides of the bag. The chevron angle D was 15 ° and the distance E between the chevron tip and the notch was 20 mm. The bag has a 6mm adhesive seal F at the cut and possibly an end gap G on the opposite side. A thumb cut-out H may be provided for opening the package to remove the auto-injector. A hanging hole I may be provided for hanging the packaged auto-injector. The hanging hole I is preferably centered 3mm from the sealed end. In this example, tear ports J are provided on both sides of the package to reduce the risk of the package failing to open for removal of the auto-injector in an emergency. The tear seam J may have a depth of about 1.6-2 mm. The peel strength of the illustrated example can be, for example, about 0.18kg/cm or 1.0 lb./inch.

Fig. 12 shows a block diagram of the method. The method comprises a method of filling a package 2 with an automatic injector comprising an epinephrine composition, package 2 comprising an opening. The size of the opening will depend on the type of device used for packaging the autoinjector. The wrapper 2 is for example a square or rectangular bag and according to some aspects the opening is located on one of the sides. The epinephrine composition may comprise a chemical oxygen scavenger. This has been discussed previously. The method comprises inserting an automatic injector into package 2 through an opening in a non-inert environment and replacing the air in package 2 with an inert atmosphere in a non-inert environment and at atmospheric pressure by one or several cycles of removing the air and filling the opening with an inert gas. The method also includes sealing the opening under vacuum. This method has the great advantage that it can be carried out in a non-inert environment. Maintaining an inert environment for packaging is very expensive and cumbersome. The process of chemically removing the oxygen and removing the air and filling with the inert gas allows filling of package 2 in a non-inert environment. Another term for removing air and injecting gas is flushing.

The material of the package 2 is preferably flexible to allow air and inert gas such as N₂And (4) effective exchange. The flexible wrapper 2 also allows integrity control of the bag by checking the "vacuum" state of the bag. The bag material should be strong enough to withstand wear of the emergency device during storage and transportation.

According to some aspects, the air is removed using a nozzle-type vacuum capper. One example of such a machine is shown in fig. 15. It has a nozzle 11, said nozzle 11 being inserted into the opening of the pack 2 and through which air is discharged. This type of machine provides a local point in the opening to remove air, which is an effective way of removing only the air in packages 2. Nozzle-type vacuum machines are known in the art and have nozzles for removing air and inflating gas through the opening of the package. The machine has a welding electrode 12, which electrode 12 is pressed down on the package to seal it at the end of the packaging process. The welding rod is preferably sealed by heating the package. The machine also has a sealing lip 13, preferably made of rubber, which lip 13 pushes the package down on and around the nozzle to maintain the seal when the nozzle removes air and injects gas. The sealing lip also pushes the package down when the nozzle is withdrawn to prevent leakage of air when withdrawn. In other words, the sealing lip keeps the package closed during the process of removing air and injecting gas, and when the process is completed, the welding wire will seal the package.

When the bag is subjected to atmospheric pressure, the machine will remove air from the bag. According to some aspects, the vacuum pressure should not be below 700mbar unless the drug container is free of air bubbles to prevent movement of the plunger. When bagging and sealing the autoinjector bag, i.e. the package 2, with a nozzle type vacuum welding machine, the opening of the bag is closed during the gas exchange and sealing process. During bagging, gas enters through the nozzle. This is achieved, for example, by the previously described sealing lip.

The length of the packages discussed previously will be affected by the type of machine used to remove the air. In a nozzle type vacuum machine, the distance between the nozzle and the auto-injector affects the air removal efficiency. The effective distance for removing air is 15-30mm, preferably 20-25 mm. When the package is sealed, if the distance is short, a problem may occur, and vacuum sealing may not be performed. Longer distances may result in inefficient air removal.

When the automatic injector (i.e. AI) is in the bag, and an inert gas (e.g. N) is used₂) Purging, and vacuum bagging using a nozzle-type vacuum capper/welder, presents two major challenges:

1) if the AI is placed too close to the end of the nozzle (within the bag), the bag mouth is forced to open at the height of the AI near the seal/weld bar, 24.4mm in one example case. Therefore, a reliable sealing process is not possible, because the risk of wrinkling due to forced widening of the bag opening is too great.

2) When the AI in the bag is too far from the end of the nozzle, the bag may prevent proper emptying of the bag through the nozzle because the bag closes between the AI and the nozzle during the suction cycle. This is negative because the necessary negative pressure (for the integrity control of the bag by the user), O, cannot be achieved₂Purging and with N₂The efficiency of the displacement is low.

For AI's having a length of 150 + -1 mm and a width of 23.4 + -0.5 mm, it has been found that the optimal distance of the AI from the nozzle is between 20 and 25 mm. Acceptable results are also achieved for a wide range of 15-30 mm.

For AI's of greater width, e.g., 40mm, a greater distance, e.g., 30-40mm, may be maintained between the AI and the nozzle. This ensures that the bag can be sealed/welded and the risk of seam wrinkling is acceptable; the bag is also opened wider to prevent the nozzle opening from being "sealed" during the suction cycle.

For AI's of smaller width, e.g., 18mm, a shorter distance, e.g., 15-20mm, may be maintained between the AI and the nozzle. This ensures that the bag can be sealed/welded and the risk of seam wrinkling is acceptable; a sufficient distance between the sealing strip and the bag deployment device (pouch-deployment device); in addition, the bag is less open and therefore a shorter distance is sufficient to prevent the nozzle opening from being "sealed" during the suction cycle.

Furthermore, the following are relevant parameters:

distance between AI and outer edge of sealing/welding bar: this is at a distance of at least 5-6cm from the AI in the bag. This parameter is related to the seal-crimp problem. If the sealing strip is too close to an AI with a width of 24.4mm, the sealing is wrinkled and therefore leaking is a major risk and a reliable sealing process cannot be performed. Longer distances between the sealing/welding bars and the AI are acceptable, but the nozzle length should then be adjusted to control the distance between the nozzle opening and the AI.

The vacuum purge and sealing process will proceed more reliably if the sealing lip (which is a rubber-like material and pushes the two sides of the bag together during the suction/blow cycle and as the nozzle is pulled from the bag, and then immediately welds) is on the other side of the sealing strip, i.e. opposite the AI, to avoid seal wrinkling. In addition, if the sealing lip is on the AI side, the bag may leak during the vacuum cycle, thus being too close to the widening effect of the AI. Thus, according to some aspects, the bag is long enough to fit the AI, leaving enough distance between the AI and the nozzle opening, as previously described, to leave enough distance between the AI and the sealing strip to stretch the open, unsealed side of the bag on the "other" side of the sealing/welding strip opposite the AI far enough to be completely covered by the sealing lip.

The exact dimensions of the bag depend on the dimensions of the sealing/welding strip and the sealing lip.

Bag size: the minimum width of the open side of the bag to be sealed/welded at the end of the vacuum packaging process may be 80-100 mm. The bag may have this width over its entire length. However, if bag material is to be minimized, a bag with an unsealed opening of 80-100mm and narrowing to the width of the AI (e.g., about 30-40mm) at a sufficient distance from the seal/weld bar may be used. Two examples of how the bag can be shaped are shown in figures 13 and 14. In fig. 13, the opening is located on the left side and has a tapered portion for reducing the width of the pouch. In fig. 14, the entire bag is tapered from the opening on the left side to the other end.

An example of a packaging process will now be described with an exemplary apparatus.

Step 1: bagging; comprising inserting an automatic injector into a bag, all but one of the sides of the bag being sealed

Step 2: displacing the air in the bag with an inert atmosphere, e.g. nitrogen, by one or more cycles of evacuating air and blowing, e.g. nitrogen

And step 3: and (5) vacuum sealing.

The bagging achieves the following effects:

remove "enough" oxygen from the interior of the bag and auto-injector and replace it with inert gas. The more oxygen removed in the process, the longer shelf life can be achieved. The data show that when the oxygen content in the bag reaches 1% or 2%, a shelf life of 36 months can be achieved. This also allows the auto-injector containing epinephrine to be stored at 40 ℃ for more than one year.

Sealing the bag to a vacuum appearance, it should be clearly seen that there is hardly any gas in the bag other than the inert gas in the auto-injector body; i.e. no air bubbles are present in the packages 2. This also allows the patient to check the integrity of the bag. If the bag loses its vacuum appearance, a hole can be assumed and the product must be replaced. This process facilitates package integrity control without the need for, for example, O in the bag₂Sensor (this is an alternative method, but does not trigger O due to packaging under inert gas₂Chemical sensors, thus making packaging more difficult).

If there is a negative pressure in the bag/AI, the gas generated by the bubbles inside the main packaging will actively (driven by the pressure difference between the main packaging (e.g. 1bar) and the bag (e.g. 700 mbar)) penetrate to the outside of the main packaging, thus a) reducing the amount of residual oxygen, B) reducing the size of the internal air bubbles and thus reducing the risk of accidental movement in flight.

For a main container containing bubbles: avoid too much negative pressure:

o during bagging-plunger movement that may affect drug sterility is avoided or minimized.

Vacuum bagging is not suitable to meet the above requirements. Vacuum chamber bagging requires that the bagging process be performed at ultra-low negative pressures in order to provide an acceptable vacuum appearance to the bag, which can result in plunger movement. The bagging process desired herein is the removal of air from the bag when the bag is at atmospheric pressure; this is disclosed in the methods discussed above.

An example of a process for providing a packaged auto-injector will now be described in more detail.

1) The prefilled syringe is filled with the drug. The syringe is not a gas-tight system (no gas-tight plunger), the needle shield is designed to be permeable to gas-to allow sterilization using ethylene oxide;

2) storing the filled syringe for 10-12 weeks;

3) after release, the syringes were assembled into autoinjectors about 12 weeks after filling, the autoinjectors were labeled and vacuum bagged:

a. the size of the bag (i.e. the wrapper) has been optimised. The bag may have a transparent portion so that the medication can be visually controlled.

i. The bag is only slightly wider than the auto-injector to minimize lofting of the bagged auto-injector. On the side of the bag where the nozzle is to be inserted, the bag is wider, for example may be wider than 80 mm.

The bag so narrowed requires venting by an auto-injector (1 change the atmosphere inside the auto-injector, 2 to let gas flow out of the other end of the narrowed bag).

The bag is significantly longer (about 70mm or longer) than the device because the auto-injector body forces the narrow bag open; this may make the welding of the bag open side unreliable (wrinkling causing the sealing weld to leak).

b. The bags were atmosphere exchanged by a nozzle type vacuum welder. Only the nozzle type can satisfy the following two requirements:

i. the vacuum during and after bagging must not be < 500mbar (otherwise plunger movement may result in reduced sterility).

Post bagging vacuum of 500mbar to about 750mbar (tbc) to give the bag vacuum feel and appearance (regulatory requirements so that the end user can control bag integrity).

c. After bagging, the bagged automatic injector and the accessory chloroprene rubber sleeve are packaged in a carton together.

Neoprene covers are used to protect the bags during transport and throughout the shelf life (3 years). The neoprene sock fits tightly around the pocketed automatic injector, which minimizes movement, thereby reducing friction and avoiding the risk of puncture. It also suppresses drop-off and temperature variations during transport by the end user.

List of markers:

1. automatic injector

2. Package

3. Opening arrangement

4. At least two holes

5. Barrier arrangement

6. Packaged auto-injector kit

7. Auto-injector body

71. First end side

72. Second end side

8. At least one through hole

81. At least one through hole opening

9. Concave part

10. Grab handle

11. Nozzle with a nozzle body

12. Welding rod

13. Sealing lip

Claims

1. A packaged autoinjector kit (6) for providing a packaged autoinjector (1) containing epinephrine, comprising:

-an at least partially transparent medicament container containing an epinephrine composition,

-a hollow auto-injector body (7) defining a space containing a medicament container, thereby forming an auto-injector (1), and

-an oxygen-impermeable package (2) for receiving an auto-injector and comprising an opening arrangement (3) for opening the package (2) for removing the auto-injector,

characterized in that the auto-injector body is provided with at least two apertures (4) provided on opposite sides of the medicament container to allow visual control of the epinephrine composition within the container, at least a portion of the package (2) is transparent to visible light to allow visual control of the epinephrine composition through the apertures (4), and the packaged auto-injector kit (6) comprises at least one blocking arrangement (5), said blocking arrangement (5) being opaque to at least ultraviolet light, the blocking arrangement (5) being arranged to prevent ultraviolet light from entering the at least two apertures (4).

2. Packaged autoinjector kit according to claim 1, wherein the at least one blocking arrangement (5) is arranged on the autoinjector body and comprises at least one film placed over the at least two holes (4), wherein the film is transparent to visible light and opaque to ultraviolet light.

3. Packaged autoinjector kit according to claim 1, wherein the at least one blocking arrangement (5) is arranged on a visible light transparent portion of the package (2) and the at least one blocking arrangement (5) comprises a layer transparent to visible light and opaque to ultraviolet light in the transparent portion.

4. Packaged autoinjector kit according to claim 1, wherein the at least one blocking arrangement (5) is arranged on the package, and wherein the transparent portion of the package is closable such that when the transparent portion is closed, the package (2) is opaque to neither the visible nor the ultraviolet light, thereby blocking the visible and ultraviolet light from entering the at least two apertures (4).

5. A packaged autoinjector kit according to claim 4, wherein the transparent portion is arranged on a first side of the package (2) and the package (2) has a second side which is opaque to both ultraviolet and visible light, wherein the blocking arrangement (5) comprises a fold of the second side of the package (2) on the first side of the package (2) to cover the transparent portion to block ultraviolet and visible light from entering the at least two apertures (4).

6. A packaged autoinjector kit according to claim 5, wherein the opening arrangement (3) is located such that the opening arrangement (3) is uncovered when the pack (2) is folded.

7. The packaged autoinjector kit according to claim 4, wherein the at least one blocking arrangement (5) comprises a flap disposed over the transparent portion, the flap adapted to be lifted to allow visual control of the pharmaceutical composition.

8. A packaged autoinjector kit according to any of the preceding claims, wherein the opening arrangement (3) is arranged to be torn by a user thereof such that the package (2) is torn, and wherein the opening arrangement (3) comprises:

-a stop preventing the user from tearing the package (2) completely, so that the package (2) remains partly when torn.

9. Packaged autoinjector kit according to any of the preceding claims, wherein the opening arrangement (3) comprises a primary opening arrangement (3') for opening the pack (2) and a secondary opening arrangement (3') for opening the pack (2) when the primary opening arrangement cannot be opened.

10. The packaged autoinjector kit according to any of the preceding claims, wherein the unopened package (2) is filled with an inert gas and is free of an oxygen trap.

11. The packaged autoinjector kit according to any of the preceding claims, wherein the epinephrine composition comprises an oxygen scavenger.

12. The packaged autoinjector kit according to any of the preceding claims, wherein the autoinjector body (7) is elongate having an elongate portion, a first end side (71) and a second end side (72) opposite the first end side (71); at least one through hole (8) is arranged through the auto-injector body (7) between the first and second end sides (71,72), whereby the at least one through hole (8) allows gas to flow through the auto-injector body (7) when the auto-injector body (7) contains a medicament container; and the encasement is a bag, the interior of the bag being at least 70mm longer than the overall length of the auto-injector, and the maximum width of the bag at the narrowest point being 30mm wider than the maximum width of the auto-injector.

13. The packaged autoinjector kit according to any of the preceding claims, wherein the package filled with the autoinjector is tightly arranged within a neoprene sleeve, thereby preventing movement of the autoinjector relative to the package.

14. A method of filling a package (2) with an automatic injector comprising an epinephrine composition, the package (2) comprising an opening, wherein the method comprises:

- (S1): inserting the automatic injector into the package (2) through the opening in a non-inert environment, and

in a non-inert environment and at atmospheric pressure:

- (S2): replacing the air in the package (2) with an inert atmosphere by one or more cycles of removing the air and filling it with an inert gas through the opening,

and

- (S3) sealing the opening under vacuum.

15. The method of claim 14, wherein air is removed using a nozzle-type vacuum capper.